Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period
Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period
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DOI：
10.1016/j.bbr.2011.01.056
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发表时间：
2011-06-01
影响因子：
2.7
通讯作者：
Brittebo, Eva B.
中科院分区：
文献类型：
--
作者：
Karlsson, Oskar;Roman, Erika;Brittebo, Eva B.
我们以前曾报道过，暴露于蓝藻神经毒素β-N-甲基氨基-L-丙氨酸（BMAA）在新生儿期导致成年大鼠的认知障碍。本研究的目的是探讨新生儿BMAA暴露对学习和记忆机制的长期影响，并确定新生儿大脑的早期形态学变化。在出生后第9-10天，在大鼠幼仔中皮下注射BMAA。BMAA（50和200 mg/kg）导致成年动物的空间学习和记忆明显缺陷，但没有形态学变化。没有发现识别记忆障碍，这表明新生儿暴露于BMAA优先影响神经元系统，是重要的空间任务。组织学检查显示，在高剂量（600 mg/kg）BMAA给药后24 h，海马中通过TUNEL染色确定早期神经元细胞死亡，而在较低剂量（50和200 mg/kg）下未观察到变化。此外，在压后和扣带皮质中有低程度的神经元细胞死亡，这些区域对认知功能也很重要。综上所述，这些结果表明，BMAA是一种发育神经毒素，诱导认知功能的长期变化。BMAA作为一种潜在的人类神经毒素所带来的风险值得进一步考虑，特别是如果拟议的食物链生物放大作用得到证实。(C)2011 Elsevier B. V.保留所有权利。
We have reported previously that exposure to the cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) during the neonatal period causes cognitive impairments in adult rats. The aim of this study was to investigate the long-term effects of neonatal BMAA exposure on learning and memory mechanisms and to identify early morphological changes in the neonatal brain. BMAA was injected subcutaneously in rat pups on postnatal days 9-10. BMAA (50 and 200 mg/kg) caused distinct deficits in spatial learning and memory in adult animals but no morphological changes. No impairment of recognition memory was detected, suggesting that neonatal exposure to BMAA preferentially affects neuronal systems that are important for spatial tasks. Histopathological examination revealed early neuronal cell death as determined by TUNEL staining in the hippocampus 24 h after a high dose (600 mg/kg) of BMAA whereas no changes were observed at lower doses (50 and 200 mg/kg). In addition, there was a low degree of neuronal cell death in the retrosplenial and cingulate cortices, areas that are also important for cognitive function. Taken together, these results indicate that BMAA is a developmental neurotoxin inducing long-term changes in cognitive function. The risk posed by BMAA as a potential human neurotoxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed. (C) 2011 Elsevier B.V. All rights reserved.